Fatty acid esters of ascorbic acid such as ascorbyl palmitate are employed in topical compositions for a varieity of purposes such as for treating and/or preventing sunburn (U.S. Pat. No. 5,409,693 to Perricone; this and all other references cited hereafter are hereby expressly incorporated herein by reference in their entireties) and for treating disorders of the skin which are caused by, or are dependent upon, depleted or inadequate collagen levels, and/or oxygen-containing free radicals, and/or oxidative generation of active metabolites via lipoxygenase pathways (U.S. Ser. No. 08/407,413 to Perricone filed Mar. 17, 1995 and allowed Jun. 11, 1996 now U.S. Pat. No. 5,574,063). Topical compositions containing acetylcholine precursors such as dimethylaminoethanol have also been disclosed for the treatment of aging skin and subcutaneous muscles; in some embodiments, the compositions also contain fatty acid esters of ascorbic acid (U.S. Pat. No. 5,554,647 to Perricone).
The compositions are efficacious because a wide variety of skin diseases and skin conditions in which the skin has undergone some form of damage or aging can be traced, either directly or indirectly, to processes which either deplete or inhibit synthesis of collagen, and/or generate oxygen-containing free radicals, and/or oxidatively generate biologically active metabolites, generally via lipoxygenase pathways, which in turn either directly act upon the skin or mediate other processes which have adverse effect on the skin. In radiation-induced skin damage, for example, particularly ultraviolet radiation-induced skin damage (e.g., sunburn), it appears that the transfer of energy from the radiation to the skin results in the generation of excited oxygen species, such as singlet oxygen, the superoxide anion, and hydroxyl radicals, that can damage lipid-rich membranes with the subsequent activation of the chemical mediators of inflammation and/or damage the skin cell membrane and DNA, and also where it appears that the radiation releases arachadonic acid which is then oxidized via two predominant pathways to produce either prostaglandins or leukotrines. Cell membranes are particularly susceptible to attack by free radicals because of their dense molecular structure largely comprising lipids and lipoproteins that are easily oxidized by reactive oxygen species and oxygen-containing free radicals. Where skin is damaged from aging or chronic exposure to sunlight, free radical-induced damage also appears to be involved and collagen content is diminished. In other disease conditions such as psoriasis, a chronic, recurrent, scaling skin disease of unknown etiology, it is possible that hydroxyeicosatetraenoic acids and leukotrines generated by oxidation of arachidonic acid via the lipoxygenase pathway have a role in the pathogenesis of the disease.
Free radical damage to the surface of the skin can be manifested as lines, mottling, discoloration, precancers and cancers. Damage to cell membranes in both epidermis and underlying subcutaneous muscle tissue can result in myriad changes including decrease of cell function, loss of cell permeability, increased intercellular ionic concentration, and decreased cellular capacity to excrete or detoxify waste products. These cause accumulation of waste products in the cells, such as lipofuscin; increase in the potassium content of the cells, which results in their dehydration; and decreased production of messenger RNA and proteins, resulting in decreased cellular repair. Some cells become so dehydrated they cannot function at all. In skin, the regularity of tissue structure is lost, and individual cells enlarge, but the total number of cells decreases approximately 30%. Intercellular collagen and elastin increases. The proportion of soluble collagen decreases, and there may be increased cross-linking between long-chain collagen macromolecules. Elastin loses its discrete structure and elasticity, and exhibits an increased calcium content.
The external appearance of aging individuals is affected not only by changes in the epidermis, but also by subcutaneous changes in underlying muscle tissue. The combination of sagging muscles and aging skin contributes to the overall cosmetic changes typically observed, such as wrinkling, which involves the transition of a formerly smooth skin surface to one that appears unevenly shrunk and/or contracted. When muscles are at rest, a certain amount of tautness usually remains. The residual degree of contraction in skeletal muscles is called muscle tone. In aging individuals, the degree of contraction relaxes, and is particularly obvious in the face. Topical application of acetylcholine precursors such as dimethylaminoethanol helps shorten subcutaneous muscles, resulting in a lift in tissue on the face, chest or other area of application.
Critical to the success of preventing and/or alleviating skin conditions or diseases or collagen deficiencies by topical treatment with fatty acid esters of ascorbic acid and treatment of subcutaneous muscle with acetylcholine precursors such as dimethylaminoethanol is the utilization of the active ingredients which are effective for the purpose without concurrent generation of adverse side effects. Equally important, however, is effective delivery to the sites where active ingredients will act most efficaciously on the disease or condition (or afford protection therefrom). Generally speaking, it is thus necessary for the active ingredients to be deliverable in either an intact form or in a form whereby the active ingredients are exposed or released in the actual environment where their activity is needed. So too, it is of importance that active ingredients be such as to be compatible with a base composition which facilitates topical application and which facilitates application in suitable dosages, and further that the active ingredients either be stable per se or have the ability to be stabilized in admixture with other components, so that preparations can be marketed with a suitably long shelf-life and such that prolonged activity can be obtained once topical application has been made.
In some cases compositions containing fatty acid esters of ascorbic acid cannot be delivered in active form and/or cannot be solubilized in base compositions and/or are unstable at the concentrations required for application and/or color the skin to which they are applied. This is particularly true of compositions containing, for example, high amounts of ascorbyl palmitate (e.g., 20% to 25% by weight), particularly where water must be used as a solvent for some of the ingredients in the formulation. Ascorbic acid is soluble in water, but insoluble in oils, fats, and fat solvents, whereas the converse is true of its fatty acid esters. The differences in solubility make it difficult to prepare compositions containing ascorbic fatty acid esters with water-soluble ingredients, including ascorbic acid. The formulations have a tendency to precipitate on storage.
Moreover, compositions containing ascorbic acid and/or its esters have a tendency to deteriorate on storage, typically by combining with oxygen in the atmosphere and/or in the aqueous solvent to yield inactive forms such as dehydro derivatives. Loss of reducing equivalents is observed, and the compositions yellow and, in extreme cases, brown.
It would be desirable to have stabilized compositions containing ascorbic acid and/or its fatty acid esters of ascorbic acid, particularly high amounts of saturated fatty acid esters.